Procaine Penicillin

Procaine penicillin (procaine benzylpenicillin) is an intramuscular depot of benzylpenicillin with intermediate duration, giving effective levels for 12 to 24 hours. It is used for susceptible streptococcal and treponemal infections where daily injection is practical and as part of regimens for neurosyphilis and congenital syphilis.

Classification. Beta-lactam, repository penicillin, combined with the local anaesthetic procaine.

Mechanism. Slow release of benzylpenicillin, which blocks cell wall synthesis.

Pharmacokinetics. Peak levels occur 1 to 4 hours after injection and stay over the MIC of susceptible streptococci for about 24 hours. Levels are higher than with benzathine penicillin and lower than with aqueous benzylpenicillin. CSF levels are adequate only with probenecid and inflamed meninges.

Deep intramuscular route only. No loading dose. Usual adult dose is 600 mg to 1.2 g (600,000 to 1.2 million units) once daily; maximum 2.4 MU daily, used for neurosyphilis.

Neurosyphilis (alternative to intravenous benzylpenicillin when outpatient treatment is possible). 2.4 MU IM once daily with probenecid 500 mg orally every 6 hours, both for 10 to 14 days.

Congenital syphilis. 50,000 units/kg IM once daily for 10 days.

Susceptible streptococcal and treponemal infections. Adults 600 mg to 1.2 g IM once daily for 7 to 10 days. Children 50,000 units/kg once daily, maximum 1.2 MU.

Alternatives. Intravenous benzylpenicillin for severe or CNS infection; benzathine penicillin for early syphilis and prophylaxis; amoxicillin or phenoxymethylpenicillin orally.

Contraindications. Penicillin hypersensitivity and hypersensitivity to procaine or other ester local anaesthetics.

Procaine reaction (Hoigne syndrome). Within minutes of injection: sudden fear of impending death, agitation, hallucinations, tachycardia, hypertension and sometimes seizures. It is not allergy and resolves in 15 to 30 minutes. Reassure, observe, and avoid mislabelling as penicillin allergy.

Other warnings. Inadvertent IV or intra-arterial injection causes embolic and gangrenous complications. Anaphylaxis and Jarisch-Herxheimer reaction occur as with other penicillins.

Interactions. Probenecid, methotrexate, oral typhoid vaccine, warfarin. Sulphonamides may be antagonised by procaine-derived para-aminobenzoic acid.

Common prescribing errors. Giving IV; treating procaine reaction as anaphylaxis and recording false allergy; using one dose of benzathine penicillin for neurosyphilis; repeating the dose with insufficient interval.

Special groups. - Pregnancy: acceptable; breastfeeding: acceptable. - Children and neonates: weight-based dosing; avoid in neonates unless benzylpenicillin is unavailable, owing to procaine load. - Older adults: usual dose. - Kidney impairment: with creatinine clearance under 10 mL/min give every 24 to 48 hours. - Liver impairment: no adjustment. - Region: used for neonatal and childhood infections where intravenous access is limited; availability varies.

Preparation. Supplied as ready suspension or powder; shake well. Deep IM into the upper outer buttock or anterolateral thigh with aspiration before injecting. Maximum 4 mL at one site in adults.

Baseline and monitoring. - Baseline: allergy history including procaine, creatinine, pregnancy test. - Syphilis: serology titres at 6, 12 and 24 months; CSF reassessment at 6 months after neurosyphilis. - Kidney function if prolonged course.

Stop rules. Stop for anaphylaxis, severe rash, or nerve injury signs. Fever after the first dose of syphilis treatment is usually Jarisch-Herxheimer.

Referral and escalation. Refer neurosyphilis, congenital syphilis, and failure to improve in 48 to 72 hours.